Evidence map›Paper›PMID 40481689›Full record

ArticleProteomics. Clinical applications2025

Bioinformatics-Based Comparative Analysis of the Human Retina Proteome.

Colin K Kim, Mak B Djulbegovic, David Broytman, Nedym Hadzijahic, Michael Antonietti, David J Taylor Gonzalez, Vladimir N Uversky, Nicolas A Yannuzzi, Carol L Karp

Abstract readComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Proteomics. Clinical applications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Colin K KimBascom Palmer Eye Institute, University of Miami, Miami, Florida, USA.ORCID 0000-0003-3729-413X
Mak B DjulbegovicWills Eye Hospital, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
David BroytmanCooper Medical School of Rowan University, Camden, New Jersey, USA.
Nedym HadzijahicBascom Palmer Eye Institute, University of Miami, Miami, Florida, USA.
Michael AntoniettiBascom Palmer Eye Institute, University of Miami, Miami, Florida, USA.
David J Taylor GonzalezBascom Palmer Eye Institute, University of Miami, Miami, Florida, USA.
Vladimir N UverskyDepartment of Molecular Medicine and USF Health Byrd Alzheimer's Research Institute, Morsani College of Medicine, University of South Florida, Tampa, Florida, USA.ORCID 0000-0002-4037-5857
Nicolas A YannuzziBascom Palmer Eye Institute, University of Miami, Miami, Florida, USA.
Carol L KarpBascom Palmer Eye Institute, University of Miami, Miami, Florida, USA.

Funding

Shared Equipment ModuleP30EY014801 · NEI · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI Victor L Perez · 2004 to 2026
$12.2M
Calvin and Flavia Oak Foundation, Dr. Tim and Cammy Ioannides GrantCarol Soffer GrantDr. Ronald and Alicia Lepke GrantEmilyn Page and Mark Feldberg GrantGrant and Diana Stanton-ThornbroughHonorable A. Jay Cristol GrantJose Ferreira de Melo GrantLee and Claire Hager GrantMichele and Ted Kaplan GrantMr. and Mrs. Irwin Friedman GrantNEI NIH HHS P30 EY014801NIH Center Core Grant P30EY014801Ragheb Family GrantRichard and Kathy Lesser GrantRichard Azar Family GrantRobert Baer Family GrantRobert Farr Family GrantRoberto and Antonia Menendez Family GrantRPB Unrestricted Award and Career Development AwardsStephen Takach GrantZvi Levin Grant
6 · The paper itself

Abstract

introductionThe human retina relies on a complex network of proteins, many of which exhibit intrinsic disorder and liquid-liquid phase separation (LLPS), enabling dynamic interactions for retinal function. Disruptions in these properties, along with missense mutations, have been linked to retinal diseases. This study aims to characterize and compare retinal proteins categorized by their expression specificity and tissue distribution using bioinformatics tools to explore relationships between intrinsic protein disorder, phase separation potential, and mutation pathogenicity.

methodsWe analyzed retinal proteins classified by the Human Protein Atlas (HPA) into two major groups based on gene expression specificity (degree of unique retinal expression) and gene expression distribution (extent of expression across tissues). We analyzed nine retinal proteomes categorized by gene expression specificity and distribution. Intrinsic protein disorder was assessed using per-residue and global disorder predictors from the Rapid Intrinsic Disorder Analysis Online (RIDAO) platform, LLPS potential was evaluated with ParSe v2, and missense mutation pathogenicity was predicted using AlphaMissense.

resultsSignificant differences in per-residue intrinsic protein disorder were found within the specificity and distribution subgroups (p < 0.0001). In addition, global disorder predictions from the RIDAO platform demonstrated non-random distributions of protein species across the proteomes analyzed in both subgroups (p < 0.0001). Furthermore, proteins specifically elevated in the retina exhibited higher intrinsic disorder and greater phase separation propensity (ParSe v2, AUC up to 0.650), compared to those more broadly expressed. Lastly, AlphaMissense analysis showed significant variations in the average pathogenicity scores of missense mutations within subgroups (p < 0.0001).

conclusionOur results show that intrinsic disorder, LLPS, and mutational tendencies are not evenly distributed among retinal proteomes. Our study demonstrates a link between intrinsic disorder, LLPS potential, and pathogenic vulnerability among retinal proteins, underscoring the unique structural and functional landscape of retinal proteomes. Proteins with higher specificity to the retina exhibit greater disorder and phase separation potential, highlighting their potential role in dynamic cellular processes that support retinal function. Conversely, proteins widely distributed across multiple tissues tend to be more ordered, suggesting a need for structural stability in their broader functional roles.

Indexed as

Computational BiologyEye ProteinsProteomeRetinaHumansMutation, MissenseRetinal DiseasesEye ProteinsProteomeAlphaMissensedeep learningHuman Protein Atlasintrinsic disorderphase separationproteomeretina

Identifiers

PMID40481689
PMCPMC12278036

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.